SUMMARY OF WORK Epidemiological studies support the view that high sodium intake and some forms of behavioral stress can contribute to the development of hypertension, and experimental studies have indicated that synergistic interactions between sodium intake and behavioral stress are sufficient to engender sustained hypertension in laboratory animals. The development of stress/salt hypertension in animals is associated with chronic suppression of breathing, and a sustained renal sodium retention which is not prevented by renal denervation. From these and related findings emerged the hypothesis that conditioned suppression of breathing can potentiate blood pressure sensitivity to high sodium intake via a cascade of responses that include sustained increases in pCO2, formation of carbonic acid, increases in hydrogen ion concentrations, increases in renal sodium-hydrogen exchange, renal sodium retention, expansion of plasma volume and increased secretion of endogenous digitalis-like factors that can inhibit sodium pump activity in vascular smooth muscle. Studies in this laboratory have shown that high resting end tidal CO2 (PetCO2) is a risk factor for blood pressure sensitivity to high sodium intake in older, and to a lesser extent, in younger, normotensive human subjects. Older subjects with high resting PetCO2 showed increased urinary excretion of endogenous digitalis-like factors which covary with plasma volume before and after sodium loading. The hypothesis that high resting PetCO2 is associated with increased resting blood pressure is being tested in a study with participants in the Baltimore Longitudinal Study on Aging. For black and white women over age 50, resting PetCO2 and systolic and diastolic blood pressure levels are positively correlated. No such associations have been observed to date in younger women, or in men. Resting PetCO2, as well as blood pressure,tends to be higher in black than white men, and higher in black than white women. Future studies will investigate the effects of increases in PetCO2 on renal functions and the association of PetCO2 with increases in blood pressure over the life span. These studies may clarify modifiable determinants of individual differences in blood pressure sensitivity to high sodium diet.